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1kits (Ebipipa 10) .
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▎ Enzimba ya AOD 9604
Ensibuko: PubChem |
Omutendera: SALLRSIPAPAGASRLLLLTGEIDLP Ensengekera ya molekyu: C 78H 123N 23O 23S2 Obuzito bwa molekyu: 1815.1g/mol Ennamba ya CAS: 221231-10-3 PubChem CID: 71300630. Enkola y’emirimu mu ggwanga |
▎ AOD 9604 Okunoonyereza
Ensibuko y’okunoonyereza eya AOD 9604 eri etya?
AOD 9604 ye peptide ekoleddwa mu kitundu kya C-terminal ekya hormone y’okukula kw’omuntu (hGH), naddala omutendera gwa amino acid 177 - 191, nga waliwo ekisigadde kya tyrosine ekirala ku N-terminus ya peptide.
Enkolagana wakati wa AOD 9604, obusimu bw’okukula, n’obujjanjabi bw’omugejjo eri bweti. Wadde ng’obusimu bw’okukula kw’omuntu (hGH) bulina obusobozi okujjanjaba omugejjo, ensonga z’obukuumi zikoma ku kugikozesa okumala ebbanga eddene. Nga C-terminal fragment ya hGH, AOD 9604 etwalibwa nti eyinza okukola omulimu mu kujjanjaba omugejjo awatali kuleeta bikolwa bibi ebya hGH. Okunoonyereza kuzudde nti hGH ne AOD 9604 zombi zisobola okuleeta okugejja n’okwongera ku lipolytic sensitivity oluvannyuma lw’okujjanjabwa okumala ebbanga eddene mu mbeba. Enkola emu esoboka kwe kuyita mu kukwatagana n’ekkubo lya β-adrenergic naddala ne beta (3)-adrenergic receptors (β3-AR) [1]. .
Bombi hGH ne AOD 9604 basobola okukendeeza ku buzito bw’omubiri n’amasavu g’omubiri gw’ebibe ebinene, era ekivaamu kino kikwatagana n’okweyongera kw’omutindo gw’okwolesebwa kwa β3-AR RNA, ekifo ekikulu ekikwata amasavu mu adipocytes. Ekikulu, byombi hGH ne AOD 9604 bisobola okwongera ku miwendo gya β3-AR RNA egyanyigirizibwa mu mbeba ennene okutuuka ku mutindo ogugeraageranyizibwa ku ogwo mu mbeba ezigonvu [1]. .
Wabula mu mbeba eza β3-AR knockout, okukozesa hGH ne AOD 9604 okumala ebbanga eddene kwalemererwa okuleeta enkyukakyuka mu buzito n’okweyongera kw’amasavu okwalabiddwa mu mbeba ez’ekika ky’omu nsiko ezifuga. Naye mu kugezesa okw’amangu, AOD 9604 eyinza okwongera ku nkozesa y’amasoboza n’okuziyiza amasavu mu mbeba ezikoona β3-AR [1]..
Obujjanjabi bw’obulwadde bw’amagumba: Empiso ya AOD 9604 mu bitundu by’omubiri (intra-articular injection) eraga ebikolwa ebimu eby’okuwonya mu nkola y’olubuto ey’obulwadde bw’amagumba. Okunoonyereza okwakolebwa Kwon Dong Rak ne Park Gi Young kulaga nti okukuba empiso ya AOD 9604 mu bitundu by’omubiri (ultrasound-guided intra-articular injection) eyamba okuddamu okukola kw’amagumba, era okukuba empiso ya AOD 9604 ne hyaluronic acid (HA) nga zigatta kikola bulungi okusinga okukozesa HA oba AOD 9604 yokka [2]. .
AOD 9604 kigambibwa nti ekoppa eby’obugagga by’obusimu obukula (lipolytic properties) eby’obusimu obukula nga tewali buzibu bwonna buva ku kuleeta ssukaali. N’olwekyo, eyinza okukozesebwa ng’eddagala eriyamba okutumbula omutindo gw’emirimu era likugirwa ekitongole ky’ensi yonna ekirwanyisa ebiragalalagala (WADA) [3]..
Ensibuko y’okunoonyereza ku AOD 9604 okusinga eva ku kukontana wakati w’obusobozi bw’obusimu bw’okukula kw’omuntu mu kujjanjaba omugejjo n’ensonga z’obukuumi bwagwo. Mu kiseera kye kimu, olw’endwadde z’enkyukakyuka mu mubiri okweyongera, omulimu gwayo oguyinza okukolebwa mu kulongoosa obulamu bw’enkyukakyuka mu mubiri n’obukuumi bwayo bifuuse ekintu ekikulu mu kunoonyereza.
Biki n’ebirungi by’enkola y’okukola kwa AOD 9604 mu kugejja n’okutereeza enkyukakyuka mu mubiri?
Okusookera ddala, mu nsonga z’okusengejja amasavu, AOD 9604 eyongera nnyo ku buwulize bw’okusengejja amasavu ng’ekola ekkubo lya β3-adrenergic receptor (β3-AR) erya adipocytes. Okukola kuno kusobozesa adipocytes okumenya obulungi triglycerides eziterekeddwa mu free fatty acids ne glycerol, bwe kityo ne kitumbula okuvunda n’okukozesa amasavu okusobola okuwa amaanyi omubiri. Enkola eno tekoma ku kuyamba kukendeeza ku kukungaanya masavu mu mubiri wabula eyamba n’okulongoosa ensaasaanya y’amasavu mu mubiri, ekendeeza ku kitundu ky’amasavu mu bitundu by’omubiri, era bwe kityo n’ekendeeza ku bulabe bw’endwadde ez’enjawulo ezeekuusa ku mugejjo, gamba ng’endwadde z’emisuwa ne sukaali ow’ekika eky’okubiri.
Ekirala, AOD 9604 nayo ekola bulungi mu kuziyiza lipogenesis. Kiyinza okuziyiza amasavu agava mu mmere eyingiziddwa okukyusibwa okufuuka amasavu g’omubiri nga kitereeza okwolesebwa kw’obuzaale obukwatagana n’okutondebwa kw’amasavu. Okusingira ddala, AOD 9604 esobola okuziyiza emirimu gy’enziyiza enkulu ezikola amasavu nga fatty acid synthase, bwe kityo ne kikendeeza ku kusengejja n’okutereka asidi z’amasavu. Kino ekiziyiza kiyamba okukendeeza ku kweyongera n’okwawukana kw’obutoffaali bw’amasavu n’okuziyiza okugaziwa okuyitiridde kw’ebitundu by’amasavu, bwe kityo ne kituuka ku kikolwa ky’okugejja. Mu kiseera kye kimu, ekikolwa kino eky’okuziyiza era kisobola okuyamba okukuuma bbalansi y’enkyukakyuka y’amasavu mu mubiri n’okwewala obuzibu mu nkyukakyuka y’emmere obuva ku kukuŋŋaanyizibwa kw’amasavu okuyitiridde.
Mu nsonga z’okulungamya enkyukakyuka mu mubiri, omulimu gwa AOD 9604 gusingako okuzibu era nga gujjuvu. Kiyinza okukyusa enkyukakyuka y’amaanyi g’omubiri okuva ku nkyukakyuka ya glucose okudda ku nkyukakyuka y’amasavu, era enkyukakyuka eno ya makulu nnyo mu kugejja n’okutumbula obulamu bw’enkyukakyuka mu mubiri. Nga eyongera ku kuvunda kwa asidi z’amasavu mu oxidative, AOD 9604 egaba ensibuko z’amaanyi amangi eri omubiri era ekendeeza ku kwesigama ku nkyukakyuka ya glucose. Enteekateeka eno ey’okukyusakyusa emmere tekoma ku kuyamba kwongera ku mutindo gwa basal metabolic rate, okufuula omubiri okukozesa amaanyi amangi nga guwummudde, naye era erongoosa enkola ya insulini, etumbula okutwalibwa n’okukozesa glucose, era bwe kityo ne kikuuma obutebenkevu bw’emiwendo gya ssukaali mu musaayi. Okugatta ku ekyo, ekikolwa kino eky’okulungamya enkyukakyuka mu mubiri era kiyamba okukendeeza ku kuteekebwa kw’amasavu mu bitundu by’omubiri ng’ekibumba, okuziyiza n’okulongoosa endwadde z’enkyukakyuka y’emmere ng’ekibumba ekirimu amasavu.
N’ekisembayo, AOD 9604 erina ebirungi eby’enjawulo mu kukendeeza ku buziyiza bwa insulini. Bw’ogeraageranya n’obusimu obukula obujjuvu, AOD 9604 eggyawo ebizibu ebiyinza okuvaako okuziyiza insulini ne ssukaali okweyongera mu musaayi. Ennongoosereza eno efuula AOD 9604 okuba ey’obukuumi mu nkola y’okujjanjaba era tegenda kubaako buzibu ku muwendo gwa sukaali mu musaayi. Kino kirina amakulu amakulu mu bujjanjabi eri abalwadde abagejjulukuka naddala abo abalina obuziyiza bwa insulini oba ssukaali mu musaayi atali wa bulijjo. AOD 9604 tesobola kubayamba kugejja kwokka wabula n’okulongoosa enkola ya insulini, okukendeeza ku bulabe bw’okufuna ssukaali ow’ekika eky’okubiri, n’okulongoosa omutindo gw’obulamu bw’omubiri okutwalira awamu.
Mu kumaliriza, AOD 9604 ekozesa ebikolwa byayo ku kugejja n’okulungamya enkyukakyuka mu mubiri ng’eyita mu nkola eziwera ez’okukola, n’ewa okulonda okupya n’essuubi erijjanjaba omugejjo n’endwadde z’enkyukakyuka mu mubiri.
Enkola ya AOD9604 ku kweyongera kw’obuzito bw’omubiri obukuŋŋaanyiziddwa obw’envunza za Zucker (fa/fa). Ebisolo ebyakeberebwa (p) byaweebwa buli lunaku ddoozi ey’omu kamwa eya 500 Ìg za AOD9604 buli buzito bw’omubiri okumala ennaku 20, ate ebisolo ebigezesebwa (P) byaweebwa obungi obwenkanankana obw’omunnyo buli lunaku mu ngeri y’emu. Ebivuddemu bitegeeza B SEM y’ebisolo 8. Enjawulo ennene ziragibwa n’akabonero k’emmunyeenye.
Ensibuko:PubMed [5] .
Biki ebikwatagana AOD 9604 mw’ayita okukosa enkyukakyuka y’amasavu?
Enkolagana n’ekkubo lya β-adrenergic: Okunoonyereza kulaga nti hGH n’akatundu ka lipolytic AOD 9604 akasengekeddwa okuva mu C-terminal yaayo bisobola okuleeta okugejja n’okwongera ku lipolytic sensitivity oluvannyuma lw’okujjanjabwa okumala ebbanga eddene mu mbeba [4] . Enkola emu esoboka kwe kuyita mu kukwatagana n’ekkubo lya β-adrenergic naddala n’ekirungo kya β3-adrenergic receptor (β3-AR). Mu mbeba ennene, hGH ne AOD 9604 zisobola okwongera ku ddaala ly’okwolesebwa kwa β3-AR RNA era zisobola okwongera ku miwendo gya β3-AR RNA egyanyigirizibwa mu mbeba ennene okutuuka ku ddaala erigeraageranyizibwa ku eryo mu mbeba ezigonvu. Wabula, obujjanjabi obw’ekiseera ekiwanvu obw’ebibe ebikoona β3-AR ne hGH ne AOD 9604 bwalemererwa okuleeta enkyukakyuka mu buzito n’okweyongera kw’amasavu okwalabiddwa mu mbeba ez’ekika ky’omu nsiko ezifuga. Naye mu kugezesa okw’amangu, AOD 9604 eyinza okwongera ku nkozesa y’amasoboza n’okuziyiza amasavu mu mbeba ezikoona β3-AR. Kino kiraga nti ebikolwa bya lipolytic ebya hGH ne AOD 9604 tebitabaganyizibwa butereevu β3-AR, wadde nga byombi bisobola okwongera ku kwolesebwa kwa β3-AR, ekiyinza oluvannyuma okuyamba okutumbula lipolytic sensitivity.
Okwongera ku oxidation y’amasavu n’okusitula lipolysis: Mu mbeba ennene (ob/ob) n’ezigonvu C57BL/6J, ebikolwa ebitawona eby’obusimu bw’okukula kw’omuntu (hGH) ne AOD 9604 (ekitundu kya C-terminal fragment of hGH) bisobola okulabibwa ku buzito bw’omubiri, bbalansi y’amasoboza, n’emiwendo gy’okukyusakyusa mu substrate. HGH ne AOD 9604 zombi zakendeeza nnyo ku buzito bw’ebibe ebinene ennyo, nga kino kyali kyekuusa ku kweyongera kw’amasavu mu mubiri n’okweyongera kw’emiwendo gya glycerol mu plasma (ekiraga nti lipolysis). Okwawukanako ne hGH, AOD 9604 tereeta sukaali mu mubiri oba okukendeeza ku kufulumya insulini. AOD 9604 tevuganya na hGH receptor era tereetera butoffaali kweyongera nga hGH. Kino kyongera okukakasa endowooza ya hGH nga prohormone, ekiraga nti akatundu ka hGH kasobola okukola mu ngeri ey’enjawulo ku kkubo ery’ennono ery’okusikirizibwa hGH [4]. .
AOD 9604 ekola ki ku kibumba?
Enkola ya AOD 9604 ku kibumba esinga kweyolekera mu nkola yaayo ey’okulungamya ku nkyukakyuka y’amasavu. Nga synthetic polypeptide ekoppa lipolytic functional domain of human growth hormone (hGH), AOD 9604 esobola okutumbula lipolysis, okuziyiza lipogenesis, n’okukyusa okukyusakyusa amaanyi g’omubiri okuva ku glucose metabolism okudda mu fat metabolism. Enkola eno ey’okukola eyamba okukendeeza ku kukuŋŋaanyizibwa kw’amasavu mu kibumba, bwe kityo ne kiwa ekibumba obukuumi ku ddaala eritali limu. Ku ndwadde z’enkyukakyuka mu mubiri ng’ekibumba ekirimu amasavu, ebikolwa by’okugejja n’okulungamya enkyukakyuka mu mubiri ebya AOD 9604 biyinza okuyamba okulongoosa embeera y’enkyukakyuka y’amasavu mu kibumba, okukendeeza ku buzito ku kibumba, era bwe kityo okulongoosa enkola y’ekibumba. Wabula mu kiseera kino waliwo okunoonyereza okutono obutereevu ku ngeri AOD 9604 gy’ekwata ku kibumba. Ebikosa ebyo waggulu okusinga biteeberezebwa okusinziira ku ngeri gye bikwata ku nkyukakyuka y’amasavu, era okunoonyereza okusingawo okwa ssaayansi kukyakwetaagisa okukakasa ebikolwa ebitongole eby’okukuuma ekibumba n’enkola y’okukola.
Makulu ki aga AOD 9604?
AOD 9604 ye polypeptide ey’obutonde ekoppa ekitundu ky’amasavu (lipolytic functional domain) eky’obusimu bw’okukula kw’omuntu (HGH), era omugaso gwayo ogw’okukozesebwa mu by’obujjanjabi gwa maanyi. Mu kujjanjaba omugejjo n’endwadde z’enkyukakyuka mu mubiri, AOD 9604 esobola bulungi okutumbula lipolysis, okuziyiza lipogenesis, n’okulungamya enkola y’omubiri mu nkyukakyuka mu mubiri, okuyamba abalwadde abagejjulukuka okugejja, okulongoosa ensengeka y’omubiri, era erina omugaso oguyinza okukozesebwa mu kujjanjaba endwadde z’enkyukakyuka mu mubiri ng’ekibumba eky’amasavu. Bw’ogeraageranya n’obusimu bw’okukula obujjuvu, buggyawo ebizibu ebiyinza okuvaako okuziyiza insulini n’okwongera ku sukaali mu musaayi, n’olwekyo kiba kya bulabe mu kiseera ky’obujjanjabi era kisaanira abalwadde ab’enjawulo.
AOD 9604 erina amakulu amakulu mu by’okunoonyereza n’okukola eddagala. Ng’eddagala erikendeeza ku mugejjo nga lirina enkola ey’enjawulo ey’okukola, liwa okulonda okupya mu kujjanjaba omugejjo, liraga obusobozi bw’eddagala lya polypeptide mu kujjanjaba endwadde z’omubiri, era liwa ebirowoozo ebipya n’endagiriro z’okunoonyereza ku kukola oluvannyuma lw’okukola eddagala erisinga okuba ery’obukuumi era erikola obulungi. Okugatta ku ekyo, okusengejja n’okunoonyereza kwa AOD 9604 kutumbula enkulaakulana y’ekitundu ky’eddagala lya polypeptide, okukakasa obusobozi bw’eddagala lya polypeptide mu kukoppa n’okulungamya emirimu egy’enjawulo egy’omubiri mu mubiri, era ne kuwa obumanyirivu obw’omuwendo mu kukola, okusengejja, n’okulongoosa eddagala lya polypeptide.
Mu kutumbula obulamu obulungi, AOD 9604 esobola okukozesebwa ng’engeri ey’obuyambi okuyamba abantu okufuga obuzito bwabwe n’okukuuma embeera ennungi. Omugejjo kizibu kya maanyi mu bantu ab’omulembe guno, era ekikolwa kyayo eky’okugejja kiyinza okuwa obuyambi obw’enjawulo eri abantu abalina obuzibu okugejja nga bayita mu mmere ennyangu n’okukola dduyiro. Mu kiseera kye kimu, nga kitereeza enkyukakyuka y’amasavu, kiyamba okulongoosa embeera y’obulamu bw’omubiri mu nkyukakyuka y’emmere, okukendeeza ku masavu mu musaayi, okukendeeza ku kutereka amasavu mu misuwa, okukendeeza ku bulabe bw’endwadde ezeekuusa ku nkyukakyuka y’omubiri ng’endwadde z’emisuwa, n’okutumbula omutindo gw’obulamu.
AOD 9604 nayo ekola kinene mu kutumbula okunoonyereza okusookerwako. Okunoonyereza kwayo kuyamba okunoonyereza ennyo ku nkola y’enkola y’obusimu bw’okukula kw’omuntu naddala omulimu gwayo ogw’enjawulo n’ekkubo ly’obubonero mu kulungamya enkyukakyuka y’amasavu. Okuyita mu kunoonyereza ku AOD 9604, bannassaayansi basobola okutegeera obulungi engeri obusimu bw’okukula gye bukolamu emirimu gyayo egy’omubiri nga bayita mu nkolagana wakati w’ebitundu ebitongole n’ebikwata, n’engeri emirimu gino gye gikyuka mu mbeera ez’enjawulo ez’omubiri n’endwadde. Okugatta ku ekyo, AOD 9604 esobola okukozesebwa ng’ekintu eky’okunoonyereza mu kunoonyereza okukwata ku nkyukakyuka y’amasavu, okuyamba bannassaayansi okunoonyereza ku nkola z’okuvunda kw’amasavu, okuzaala, n’okukyusa obubonero bw’obutoffaali, okubikkula enkola za molekyu n’emikutu gy’okulungamya enkyukakyuka y’amasavu, n’okuwa omusingi gw’enzikiriziganya ogw’okukola enkola z’obujjanjabi n’eddagala ly’okukyusakyusa amasavu mu ngeri etaali ya bulijjo.
Omuwandiisi wa Journal
Heffernan, MA alina akakwate ne Yunivasite y’e Limerick era akola nnyo mu by’ensoma ebiwerako. Mu bino mulimu Endocrinology & Metabolism, okunoonyereza gye kuyinza okussa essira ku nkola y’obusimu n’enkola y’okukyusakyusa ebiriisa mu mubiri. Mu Sayansi wa Polymer, omulimu gwabwe guyinza okuzingiramu okunoonyereza ku bintu bya polimeeri, okusengejja kwabyo, eby’obugagga byabwe, n’okubikozesa. Physiology yandibadde ekwata ku mirimu n’enkola z’ebiramu, ate Nutrition & Dietetics ekwata ku ssaayansi w’emmere, endya, n’enkola z’emmere.
Ebikwata ku Muwandiisi
Ebintu ebyogeddwako waggulu byonna binoonyerezeddwako, birongooseddwa era ne bikung’aanyizibwa kkampuni ya Cocer Peptides.
Omuwandiisi wa Scientific Journal
Okunoonyereza kwa Heffernan kuyinza okunoonyereza ku nkulungo z’ennimiro zino, gamba ng’okukola enkola z’okutuusa eddagala ezesigamiziddwa ku polimeeri eri obuzibu mu nkyukakyuka y’emmere oba okunoonyereza ku bikolwa by’omubiri eby’okuyingira mu mubiri nga bakozesa obukodyo obw’omulembe obwa ssaayansi w’ebintu. Omulimu gwabwe guyamba okutegeera ennyo enkola z’ebiramu n’okukola eby’okugonjoola ebiyiiya mu by’obulamu ne ssaayansi w’ebintu. Heffernan, MA awandiikiddwa mu kiwandiiko ekijuliziddwa [4].
